The fetus of a diabetic mother (FDM) is at increased risk for morbidity and mortality. Although it is acknowledged that these risks relate directly or indirectly to various metabolic problems associated with maternal carbohydrate intolerance, the precise mechanisms which underlie poor outcome in FDM are not understood clearly. We plan to study in chronic sheep diabetes models a complex of related fetal metabolic and neural and hormonal factors. Our own work and the work of others have shown hypoxemia to be a characteristic feature of experimental hyperinsulinemia and hyperglycemia in fetal sheep. We propose to study the potential roles of certain fetal neural and hormonal factors (sympathoadrenal, thyroid, and adrenocortical) in mediating this hypoxemia. In fetal sheep with chronic peripheral catheters and a chronic adrenal cannula, we will observe the states of these neural and hormonal systems in concurrence with the hypoxemia of altered fetal glucose-insulin metabolism. Further, we will observe the effects of individual ablation of these systems on fetal oxygenation and metabolism in response to maternal diabetes. Both clinical and experimental evidence suggests a harmful effect of uncontrolled maternal diabetes on the development of the endocrine pancreas in the fetus. In this area we plan to study the effect of streptozocin-induced diabetes in pregnant ewes on the insulin secretory function of the fetus.